GROWTH RESEARCH PROGRAMME


Introduction

Early life nutrition is critical for healthy development. Breastfeeding improves survival, health, and development of all children. However, breastfeeding is no longer a norm in many communities. Currently only about 36% of infants aged 0-6 months worldwide had been breastfed exclusively. Even in most high-income countries, the prevalence of breastfeeding is below 20%. Findings from epidemiological studies substantiate the fact that the decision to not breastfeed a child has major long-term effects on the health, nutrition and development of the child and on women’s health. In the past two decades it is demonstrated that crucial programming events that are modulated during breastfeeding can have protective lifelong effects for the infant. These events might be mediated directly by or through effects on the infant microbiome. The ability of the microbiome to regulate host responses in infancy depends on individual bacterial species, immune regulation and metabolic responses. The interplay between nutrition, gut microbiota, and its large number of metabolic and immune mediators plays an essential role in the development of gut immune homeostasis in early life. This interaction needs to be better understood because a disturbed immune function in the neonatal period is harmful for neonatal survival and enhances the risk of chronic inflammatory disease later in life. In particular, preterm infants are at risk because of their immature gut and an associated intestinal state of dysbiosis, due to repeated administration of antibiotics as part of routine clinical practice following preterm birth.



Objectives

The objective of GROWTH is to set-up a new European platform that trains young scientists in the industry-led exploration of innovative routes to fully exploit the potential of early life nutrition to prevent inflammatory disease. GROWTH puts forward four research aims that will equip young scientists with a unique blend of scientific competences during their doctoral programme:

- To define the metabolic components in breast milk that directly modulate gut epithelia or mucosal immune cells, and which in turn protect infants from conditions such as sepsis or NEC.

- To provide functional insights into the microbiota dysbiosis associated with preterm birth and to establish the role played by the gut microbiome in the metabolism of both breast milk and nutritional supplements provided in early life.

- To define bioactive microbial co-metabolites generated from intestinal or endogenous compounds that affect epithelia or mucosal immune cells in the gut, in relation to intestinal pathology.

- To analyse the metabolic profile data of longitudinally collected faecal samples and develop novel bioinformatics approaches for studying microbiome-host-nutritional interactions in large scale omics data sets that allow for biomarker discovery and stratification of dietary interventions in neonates and preterm infants.


Eight Individual Research Projects

To progress beyond the state-of-the-art in early life nutrition and (chronic) intestinal disease, a new generation of innovation-minded researchers is needed who are able to tackle present challenges and develop effective solutions for early detection of disease and development of new dietary interventions for the prevention of intestinal failure in preterm infants and colitis later in life. GROWTH’s proposition is to create a network of young professionals, who

(1) have an in-depth, yet wide understanding of the field of early life nutrition in relation to intestinal inflammatory disease.

(2) are able to explore and translate pathogenic insights.

(3) are confident in applying state-of-the-art tools and knowledge necessary to concretize clinical developments, including in vitro, in vivo and ex vivo models.

(4) accelerate the identification of predictive biomarkers and the development of novel nutritional formulae.

(5) have open data science as well as enthusiastic industrial and regulatory mind-sets.

At the same time, the deep industry-academia blended training will prepare the students to fast forward their career in health and life sciences across academic and industry sectors.


Research approach

The overall research approach represents a central pipeline of activities from metabolomics and microbiota and mycobiota sequencing for biomarker discovery and bio-analytical method development, and elucidating biological mechanisms for target/drug discovery for personalized nutritional interventions in which industry-academic training is provided. Additionally, intensive intersectoral collaboration within and between each WP will provide strong synergy to embark on scientific challenges and adequately prepare the fellows for larger-scale collaborations.

GROWTH is subdivided into 2 research directions:

1. Development of ultra-performance liquid chromatography - tandem mass spectrometer-based assays for the quantitative analysis of target metabolites. With this functional metabolic analysis of the neonatal gut microbiome and associated pathobionts will be identified. Also (un)targeted analysis of the faecal metabolome and development of bio-informatics approaches will be pursued for mapping the microbiome and mycobiome and their metabolomic functions.

2. Study how the ecology of the gut microbiome is constructed during the first stages of life. Here, key microbiome and metabolomic interactions will be mapped to determine key components of nutritional interventions that influence its development and in turn the maturation of the innate immune system. A metabolic phenotype for intestinal failure (including sepsis and necrotizing enterocolitis) will be established with which the role of these multifactorial disease pathways will be studied. Advanced microfluidic gut-on-a-chip model systems, enteric glial cells and epithelial co-cultured mini-gut organoids, as well as replicable animal models will be developed to study the mechanism of action and deliver therapeutic targets for novel nutritional formulae.